8f8y: Difference between revisions

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-'''Unreleased structure'''
-The entry 8f8y is ON HOLD
+==PHF2 (PHD+JMJ) in Complex with VRK1 N-Terminal Peptide==
+<StructureSection load='8f8y' size='340' side='right'caption='[[8f8y]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8f8y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8F8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F8Y FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8f8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f8y OCA], [https://pdbe.org/8f8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f8y RCSB], [https://www.ebi.ac.uk/pdbsum/8f8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f8y ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PHF2_HUMAN PHF2_HUMAN] Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.<ref>PMID:21532585</ref> <ref>PMID:20129925</ref> <ref>PMID:21167174</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 (H3K4me3) and methylated non-histone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR(2)TK(4)) and VRK1 (PR(2)VK(4)) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (K(D) values) of 160 nM and 42 nM, respectively, which are 4x and 21x lower (and higher affinities) than for the isolated PHD domain of PHF2. X-ray crystallography revealed that the K4me3-containing peptide is positioned within the PHD and Jumonji interface, with the positively charged R2 residue engaging acidic residues of the PHD and Jumonji domains, and with the K4me3 moiety encircled by aromatic residues from both domains. We suggest that the micromolar binding affinities commonly observed for isolated methyl-lysine reader domains could be improved via additional functional interactions within the same polypeptide or its binding partners.
-Authors:
+A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2.,Horton JR, Zhou J, Chen Q, Zhang X, Bedford MT, Cheng X J Biol Chem. 2022 Dec 31:102862. doi: 10.1016/j.jbc.2022.102862. PMID:36596360<ref>PMID:36596360</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8f8y" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cheng X]]
+[[Category: Horton JR]]